Ketamine 

1. Overview

Ketamine is a  produce dissociative anesthesia—a unique state with:

• Analgesia
• Amnesia
• Preserved airway reflexes
• Sympathomimetic effects

Unlike other sedatives, ketamine does NOT cause significant respiratory depression (key ICU advantage).

2. Mechanism of Action

Primary:

• NMDA receptor antagonism → ↓ excitatory neurotransmission (glutamate)

Secondary:

• Opioid receptor interaction → analgesia
• Monoaminergic effects → ↑ catecholamines

3. Pharmacokinetics

Parameter	Details
Route	IV, IM, oral, intranasal
Onset	IV: 30–60 sec
Duration	5–15 min (bolus)
Distribution	Highly lipophilic
Metabolism	Hepatic (CYP450) → norketamine (active)
Elimination	Renal

 Accumulation in prolonged infusion → delayed recovery

4. Pharmacodynamics

CNS

• Dissociative anesthesia (thalamo-cortical dissociation)
• ↑ cerebral blood flow (CBF), ↑ cerebral metabolic rate (CMRO₂)
• Historically thought ↑ ICP (now controversial—safe in controlled ventilation)

Cardiovascular

• ↑ HR, ↑ BP, ↑ CO (sympathomimetic)
• Direct myocardial depressant (masked unless catecholamine depleted)

Respiratory

• Bronchodilation 
• Minimal respiratory depression
• Preserves airway reflexes

5. ICU Indications

 1. Induction Agent (RSI)

• Preferred in:
• Hemodynamic instability
• Trauma
• Septic shock
• Dose:IV: 1–2 mg/kg

 2. Sedation in ICU

• Especially in:
• Hypotensive patients
• Difficult-to-sedate patients
• Infusion:0.5–2 mg/kg/hr

3. Analgesia (Opioid-sparing)

• Low-dose infusion:0.1–0.3 mg/kg/hr
• Useful in:
• Postoperative pain
• Opioid tolerance
• Hyperalgesia

4. Status Asthmaticus

• Severe bronchospasm refractory to standard therapy
• Dose:Bolus: 0.5–1 mg/kg
• Infusion: 0.5–2 mg/kg/hr

 Causes bronchodilation + reduced airway resistance

 5. Refractory Status Epilepticus

• NMDA blockade helps when GABA drugs fail

 6. Procedural Sedation

• Short ICU procedures:
• Chest tube
• CVC insertion
• Dressing

 7. Adjunct in ARDS

• Facilitates:
• Ventilator synchrony
• Reduced opioid requirement

6. Dosing Summary 

Indication	Dose
RSI	1–2 mg/kg IV
Sedation infusion	0.5–2 mg/kg/hr
Analgesia (low dose)	0.1–0.3 mg/kg/hr
Status asthmaticus	0.5–1 mg/kg bolus + infusion
IM (emergency)	4–5 mg/kg

7. Adverse Effects

CNS

• Emergence delirium (hallucinations, nightmares)
• ↑ ICP (controversial; minimal with ventilation)

Cardiovascular

• Hypertension, tachycardia

Respiratory

• Hypersalivation → risk of laryngospasm

Others

• Nausea/vomiting
• Increased intraocular pressure (IOP)

8. Contraindications / Cautions

Absolute (relative in ICU):

• Uncontrolled hypertension
• Aortic dissection

Relative:

• Ischemic heart disease
• Severe psychiatric disorders
• Raised ICP (traditional teaching—now evolving)

9. Ketamine in Traumatic Brain Injury (TBI) – Updated Concept

Old belief: increases ICP
Current evidence (Brain Trauma Foundation / modern ICU data):

• Safe if:
• Normocapnia maintained
• Adequate sedation
• May improve cerebral perfusion pressure (CPP)

10. Ketamine vs Other Sedatives 

Feature	Ketamine	Propofol	Midazolam
BP	↑	↓↓↓	↓
Respiration	Minimal depression	Severe depression	Moderate
Analgesia	Yes	No	No
Bronchodilation	Yes	No	No
ICP	Neutral/slight ↑	↓	↓